Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

M proteins are receptor proteins and one of the virulence factors of streptococci. M proteins seem to play a role in inflammatory skin disorders such as psoriasis. It is however unknown whether M proteins have a direct influence on proliferative activity of human keratinocytes. In the present study human HaCaT keratinocytes were exposed to M proteins (M1, M3, M5, M12) and the proliferative and proinflammatory response was analyzed. We found a dose-dependent inhibition of keratinocyte proliferation with crude extract of strain M3 4/55. Following affinity chromatography we found inhibitory activity for keratinocyte proliferation with a maximum of 80% at 10-8 M in the M protein. Additionally tested M1 protein preparation showed an inhibitory activity of 55% whereas other M preparations (5 and 12) did not show any effect. In supernatants from HaCaT cultures IL-1alpha, IL-1beta, IL-6, IL-8, TNFalpha and ICAM-1 were measured by ELISA. The levels of IL-8 were high and TNFalpha was upregulated, whereas ICAM-1 was decreased from around 20 ng/ml to almost zero. In contrast to the streptococcal-derived M3 protein preparation the recombinant M3 did not interfere with the proliferation of HaCaT cells. Because neither recombinant M3 protein nor M3 protein purified by ion exchange chromatography on a Q-resource column had any antiproliferative activity on keratinocytes we suggest, that a component different from M3 protein was responsible.
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PMID:Keratinocyte growth inhibition by streptococcal proteins. 985 94

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.
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PMID:Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo. 985 39

Inflammatory response in tissue results from a complex network of interactions between inflammatory cells (mast cells, eosinophils, basophils, macrophages) and resident cells belonging to the lung structure (like endothelial cells, fibroblasts, epithelial cells). Among structural cells, endothelial cells play a critical role. The important role of endothelium is also reflected in the fact that it occupies an area exceeding 1000 m2. Thus, endothelium is the largest and the most active paracrine organ in the body, producing potent vasoactive, procoagulant, anticoagulant, and proinflammatory substances. Endothelial cells have four key functions that alter in the process of inflammation: 1 a) Regulation and control of leukocyte traffic through the expression of adhesion molecules (selectins E and P, molecules of immunoglobulin superfamily ICAM-1, ICAM-2, VCAM); 1 b) They are also able to amplify leukocyte activation through the production of proinflammatory cytokines like IL-1, IL-6 and chemokines like IL-8 and RANTES molecules; 2) Regulation of vascular tone by production of PGI-2, EDRF/NO and elements of local renin-angiotensin system; 3) Regulation of local coagulation by controlling the production of t-PA and PAI-1; 4) Regulation of the vascular permeability. In the states of acute inflammation, the endothelial cell takes on a proinflammatory phenotype and as such becomes chemoattractant, facilitating leukocyte adhesion, activation and migration, becomes prothrombotic and demonstrates enhanced vascular permeability.
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PMID:[The role of endothelial cells in allergic inflammation reactions]. 986 70

Recent evidence suggests that mucosal epithelial cells are capable of actively participating in immune reactions via expression of surface antigens, such as adhesion molecules, and synthesis of cytokines. This appears to be important in the pathophysiology of non-ocular allergic disorders. The objectives of the experiments were to compare the expression of HLA-DR, ICAM-I and pro-allergic cytokines in conjunctival epithelial cells in the different chronic ocular allergic disorders with each other and with normal subjects. Conjunctiva from normal patients (n=10) and patients with vernal keratoconjunctivitis (VKC, n=10), atopic keratoconjunctivitis (AKC, n=10) and contact lens-associated giant papillary conjunctivitis (GPC, n=10) were examined by immunohistochemistry. Epithelial cell staining for surface antigens and cytokines was graded by one masked observer using a four point scale based on the percentage of epithelial cells staining positive. There was no expression of ICAM-1 or HLA-DR in the normal conjunctival epithelial cells, but both antigens were induced on conjunctival epithelial cells in the allergic tissue, and there was greater expression in AKC and VKC compared with GPC. Cytokines IL-6, IL-8, RANTES and TNF-alphaall localised to normal conjunctival epithelial cells. RANTES was upregulated in all the allergic disorders and IL-8 was upregulated in GPC. IL-3 and GM-CSF were not expressed in normal conjunctival epithelial cells. GM-CSF was expressed in all disorders and there was greater expression in AKC compared with GPC and VKC. IL-3 was expressed only in AKC and VKC epithelial cells. These results suggest that conjunctival epithelial cells play an important pro-inflammatory role in chronic ocular allergic diseases; ICAM-1 may allow epithelial cells to recruit, retain and locally concentrate leukocytes; the presence of HLA-DR raises the question of conjunctival epithelial cell antigen presentation. The epithelial cytokines which are upregulated are known to promote eosinophilic inflammation and are typical of allergic inflammation. The differences in cytokine patterns may be exploitable for future therapy.
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PMID:The role of conjunctival epithelial cells in chronic ocular allergic disease. 987 10

Gene transfer to the ocular surface epithelium is of potential therapeutic value. It was determined whether a reporter gene can be introduced into the ocular surface epithelium in vitro (human cell lines), ex vivo (human tissues), and in vivo (rats) by treating with a recombinant, replication-deficient, adenovirus type 5. Human and conjunctival cell lines were cultured with various multiplicities of infection (MOI; 3.2x10(-5)-5x10(-1)) of adenovirus vector (Ad5:Adex1CAlacZ) containing the reporter gene lacZ (1.3-2.0x10(4) PFU ml-1). The ex vivo study used human corneal and conjunctival tissues obtained from an eye bank and during surgery. Non-specific upregulation of inflammatory cytokines of conjunctival epithelium infected by Ad5 was assayed and its suppression by steroids. For the in vivo study, Ad5 (5x10(5) PFU, 5-10 microliter) was applied to the eyes of 8-12-week-old cotton rats, which were enucleated 24 and 48 hr later. The maximum lacZ expression in vitro was demonstrated in the corneal epithelial cell line at 7 days (1x10(-1) MOI) and conjunctival epithelial cell line at 2 days (4x10(-4) MOI). Furthermore, lacZ was also expressed in the superficial corneal and conjunctival epithelium in the ex vivo study. IL-6, IL-8, and ICAM-1 expression from conjunctival epithelium by Ad5 was significantly inhibited by treatment with betamethasone (BM). For the in vivo study, only the conjunctival epithelium demonstrated beta-Gal activity at 24 and 48 hr after application. These data indicate that adenovirus vector is capable of directly delivering gene to the corneal and conjunctival epithelium, suggesting a variety of possible gene therapy uses. The concomitant application of steroid eye drops may avoid inflammation.
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PMID:Adenovirus-mediated gene transfer to the ocular surface epithelium. 987 15

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNF alpha), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4-6 h after the start of CPB.
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PMID:Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits. 988 89

We evaluated the relative contribution of ICAM-1 and ICAM-2, known ligands on endothelium for LFA-1 and Mac-1, in spontaneous neutrophil (PMN) transendothelial migration (TEM) across IL-1-activated HUVEC monolayers or TEM induced by C5a or IL-8 across unstimulated HUVEC grown on polycarbonate filters. Adhesion blocking mAb to ICAM-1 [R6.5 F(ab)2] or ICAM-2 [CBR IC2/2 F(ab)2] tended to inhibit TEM under each condition but, in general, inhibition was significant only with both ICAM-1 and ICAM-2 blockade. mAb to LFA-1 partially inhibited migration to C5a or IL-8 across unstimulated HUVEC and inhibition was not altered by additional treatment of HUVEC with mAbs to ICAM-1 and -2. In contrast, with IL-1 HUVEC, mAb to ICAM-1 significantly inhibited this LFA-1-independent TEM. mAb to Mac-1 alone partially inhibited TEM and, when combined with mAb to LFA-1, migration was almost completely blocked with all TEM conditions tested. The contribution of alternate ligands for Mac-1 in mediating Mac-1-dependent but ICAM-1/-2-independent C5a-induced TEM was examined using anti-LFA-1-treated PMN and anti-ICAM-treated resting HUVEC. Addition of RGD peptides, fibronectin, fibrinogen, heparins, collagens alone or in combination, even to heparinase-treated HUVEC, did not inhibit this Mac-1-mediated PMN TEM. The results indicate that: (1) LFA-1 mediates PMN TEM primarily by interaction with ICAM-1 and ICAM-2; (2) ICAM-2 may function in concert with ICAM-1 in this role, especially on unstimulated endothelium, and (3) Mac-1 on PMN also plays a major role in TEM and can utilize yet to be identified ligands distinct from ICAM-1 or -2, especially on unstimulated endothelium.
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PMID:Role of ICAM-1 and ICAM-2 and alternate CD11/CD18 ligands in neutrophil transendothelial migration. 988 54

Endothelial cell dysfunction is a classic consequence of radiation damage. Bone marrow endothelial cells (BMEC) are a critical component of the stroma in the regulation of haemopoiesis. In animal models, radiation-induced injury of BMEC has been described and a role for BMEC in haemopoietic regeneration after irradiation has been suggested. However, functions of BMEC involved in the haemopoietic regeneration have not been assessed. Therefore we studied the functional response of human BMEC to irradiation using the transformed human BMEC line (TrHBMEC) irradiated with 2. 5 or 10Gy. Our results showed a time- and a dose-dependent increase in damage to irradiated TrHBMEC measured by a decreased number of adherent cells which correlated with increased apoptosis and augmented release of soluble ICAM-1 and von Willebrand factor. 2 Gy irradiated TrHBMEC expressed more ICAM-1 on their surface than non-irradiated cells, whereas no change in VCAM-1, E-selectin and PECAM-1 expression was observed. An increased production of G-CSF, GM-CSF, IL-8, IL-6, IL-1alpha, IL-11, MIP-1alpha and SCF and no production of LIF, TNF-alpha, TPO and IL-3 by 2 Gy irradiated TrHBMEC was observed. The haemopoietic supportive function of TrHBMEC was not altered after a 2 Gy exposure. These results suggest that although radiation induces endothelial cell damage, irradiated cells still support the proliferation and the differentiation of CD34+ haemopoietic cells.
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PMID:Characterization of the response of human bone marrow endothelial cells to in vitro irradiation. 988 9

IL-17 is a novel T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated whether hapten-specific T cells isolated from patients with allergic contact dermatitis (ACD) to nickel produce IL-17 and the effects of IL-17 alone or in combination with IFN-gamma or TNF-alpha on the immune activation of keratinocytes. Skin affected with ACD to nickel and skin-derived, nickel-specific CD4+ T cell lines expressed IFN-gamma, TNF-alpha, and IL-17 mRNAs. Four of seven nickel-specific CD4+ T cell clones positive for the skin-homing receptor, cutaneous lymphocyte-associated Ag, were shown to corelease IL-17, IFN-gamma, and TNF-alpha. In contrast, two nickel-specific CD8+ T cell clones failed to synthesize IL-17. Normal human keratinocytes were found to express constitutively the IL-17 receptor gene. IL-17 specifically and dose-dependently augmented IFN-gamma-induced ICAM-1 expression on keratinocytes at both the mRNA and the protein level, whereas HLA-DR, MHC class I, and CD40 levels were not modulated by IL-17. On the other hand, IL-17 alone did not affect ICAM-1 or enhance TNF-alpha-induced ICAM-1. In addition, IL-17, both directly and in synergism with IFN-gamma and/or TNF-alpha, stimulated synthesis and release of IL-8 by keratinocytes. In contrast, IFN-gamma- and TNF-alpha-induced production of RANTES was markedly inhibited by IL-17, and the synthesis of macrophage chemotactic protein 1 was not changed. Taken together, the results suggest that IL-17 is an important player of T cell-mediated skin immune responses, with synergistic or antagonist effects on IFN-gamma- and TNF-alpha-stimulated keratinocyte activation.
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PMID:IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. 988 25

The effect of cardiopulmonary bypass (CPB) on various blood parameters in children undergoing major cardiovascular surgery was investigated in a prospective clinical study. Blood samples of children with CPB (CPB group, n = 18) or without CPB (control, n = 12) were collected before, during, and after surgery. The concentration of routine laboratory parameters, components of the complement system (C3, C4, C5, C1 inhibitor, total hemolytic complement, C3d, and C5a), circulating interleukins (IL-6 and IL-8) and soluble adhesion molecules (sICAM-1 and sE-selectin) were determined. In both groups of patients the serum concentrations of C3, C4, C5, and C1 inhibitor were significantly affected by the treatments (p < 0.001), decreased immediately after onset of anesthesia, were minimal during surgery, and increased thereafter. No significant differences in the kinetics of these parameters were detectable between CPB and control group. In the CPB group the activation of the alternative pathway (increased C3d) was found to be a specific response (p = 0.005), but also in the control group C3d and C5a concentration increased significantly (p < 0.022), indicating complement activation. None of the effects that would be expected after activation of the complement system were specific for the CPB group. In both groups the serum levels of IL-6 increased dramatically during and/or after surgery (p = 0.001), and IL-8 was detectable after surgery in 10/12 control patients. The concentration of sICAM-1 and sE-selectin decreased during surgery (p < 0.04) and later did not increase above baseline. Our data suggest that increased serum levels of inflammation mediators and increased consumption of complement and adhesion molecules occur during cardiovascular surgery. Although complement activation and ICAM-1 consumption are more pronounced in the CPB patients, none of these changes occurs exclusively in the CPB group. We conclude, therefore, that these changes are the combined effect of anesthesia, surgical trauma, and endothelial lesions. Additional, undefined CPB-induced reactions may also contribute the postoperative morbidity.
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PMID:Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass. 998 87


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